tbuckley/cabot-search huggingface dataset:
Endocannabinoid signaling in adult hippocampal neurogenesis: A mechanistic and integrated perspective
Authors: Sergio Oddi, Maria Teresa Fiorenza, Mauro Maccarrone
Journal: Progress in Lipid Research (2023)

Dentate gyrus of the hippocampus continuously gives rise to new neurons, namely, adult-born granule cells, which contribute to conferring plasticity to the mature brain throughout life. Within this neurogenic region, the fate and behavior of neural stem cells (NSCs) and their progeny result from a complex balance and integration of a variety of cell-autonomous and cell-to-cell-interaction signals and underlying pathways. Among these structurally and functionally diverse signals, there are endocannabinoids (eCBs), the main brain retrograde messengers. These pleiotropic bioactive lipids can directly and/or indirectly influence adult hippocampal neurogenesis (AHN) by modulating, both positively and negatively, multiple molecular and cellular processes in the hippocampal niche, depending on the cell type or stage of differentiation. Firstly, eCBs act directly as cell-intrinsic factors, cell-autonomously produced by NSCs following their stimulation. Secondly, in many, if not all, niche-associated cells, including some local neuronal and nonneuronal elements, the eCB system indirectly modulates the neurogenesis, linking neuronal and glial activity to regulating distinct stages of AHN. Herein, we discuss the crosstalk of the eCB system with other neurogenesis-relevant signal pathways and speculate how the hippocampus-dependent neurobehavioral effects elicited by (endo)cannabinergic medications are interpretable in light of the key regulatory role that eCBs play on AHN.
Fossilisation processes and our reading of animal antiquity
Authors: Ross P. Anderson, Christina R. Woltz, Nicholas J. Tosca, Susannah M. Porter, Derek E.G. Briggs
Journal: Trends in Ecology & Evolution (2023)

Estimates for animal antiquity exhibit a significant disconnect between those from molecular clocks, which indicate crown animals evolved ∼800 million years ago (Ma), and those from the fossil record, which extends only ∼574 Ma. Taphonomy is often held culpable: early animals were too small/soft/fragile to fossilise, or the circumstances that preserve them were uncommon in the early Neoproterozoic. We assess this idea by comparing Neoproterozoic fossilisation processes with those of the Cambrian and its abundant animal fossils. Cambrian Burgess Shale-type (BST) preservation captures animals in mudstones showing a narrow range of mineralogies; yet, fossiliferous Neoproterozoic mudstones rarely share the same mineralogy. Animal fossils are absent where BST preservation occurs in deposits ≥789 Ma, suggesting a soft maximum constraint on animal antiquity.
Significance of Degree of HLA Disparity Using T-cell Replete Peripheral Blood Stem Cells From Haploidentical Donors With Posttransplantation Cyclophosphamide in AML in First Complete Hematologic Remission: A Study of the Acute Leukemia Working Party of the EBMT
Authors: Mohamed A. Kharfan-Dabaja, Myriam Labopin, Ernesto Ayala, Ali Bazarbachi, Didier Blaise, Jan Vydra, Stefania Bramanti, Maija Itälä-Remes, Christoph Schmid, Alessandro Busca, Edouard Forcade, Werner Rabitsch, Marco Zecca, Nicolaus Kröger, Claude-Eric Bulabois, Giovanni Grillo, Alessandro Rambaldi, Renato Fanin, Francesco Zallio, Nicola Di Renzo, Yener Koc, Yana Novis, Andrew McDonald, Concepcion Herrera Arroyo, Jaime Sanz, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
Journal: HemaSphere (2023)

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2-3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2-3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2-3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2-4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2-3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.
Hepatic retinaldehyde deficiency is involved in diabetes deterioration by enhancing PCK1- and G6PC-mediated gluconeogenesis
Authors: Hanyu Yang, Mengxiang Su, Ming Liu, Yun Sheng, Liang Zhu, Lu Yang, Ruijing Mu, Jianjun Zou, Xiaodong Liu, Li Liu
Journal: Acta Pharmaceutica Sinica B (2023)

Type 2 diabetes (T2D) is often accompanied with an induction of retinaldehyde dehydrogenase 1 (RALDH1 or ALDH1A1) expression and a consequent decrease in hepatic retinaldehyde (Rald) levels. However, the role of hepatic Rald deficiency in T2D progression remains unclear. In this study, we demonstrated that reversing T2D-mediated hepatic Rald deficiency by Rald or citral treatments, or liver-specific Raldh1 silencing substantially lowered fasting glycemia levels, inhibited hepatic glucogenesis, and downregulated phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) expression in diabetic db/db mice. Fasting glycemia and Pck1/G6pc mRNA expression levels were strongly negatively correlated with hepatic Rald levels, indicating the involvement of hepatic Rald depletion in T2D deterioration. A similar result that liver-specific Raldh1 silencing improved glucose metabolism was also observed in high-fat diet-fed mice. In primary human hepatocytes and oleic acid-treated HepG2 cells, Rald or Rald+RALDH1 silencing resulted in decreased glucose production and downregulated PCK1/G6PC mRNA and protein expression. Mechanistically, Rald downregulated direct repeat 1-mediated PCK1 and G6PC expression by antagonizing retinoid X receptor α, as confirmed by luciferase reporter assays and molecular docking. These results highlight the link between hepatic Rald deficiency, glucose dyshomeostasis, and the progression of T2D, whilst also suggesting RALDH1 as a potential therapeutic target for T2D.
Bioprinting Methods for Fabricating In Vitro Tubular Blood Vessel Models
Authors: Seon-Jin Kim, Min-Gyun Kim, Jangho Kim, Jessie S. Jeon, Jinsoo Park, Hee-Gyeong Yi
Journal: Cyborg and Bionic Systems (2023)

Dysfunctional blood vessels are implicated in various diseases, including cardiovascular diseases, neurodegenerative diseases, and cancer. Several studies have attempted to prevent and treat vascular diseases and understand interactions between these diseases and blood vessels across different organs and tissues. Initial studies were conducted using 2-dimensional (2D) in vitro and animal models. However, these models have difficulties in mimicking the 3D microenvironment in human, simulating kinetics related to cell activities, and replicating human pathophysiology; in addition, 3D models involve remarkably high costs. Thus, in vitro bioengineered models (BMs) have recently gained attention. BMs created through biofabrication based on tissue engineering and regenerative medicine are breakthrough models that can overcome limitations of 2D and animal models. They can also simulate the natural microenvironment in a patient- and target-specific manner. In this review, we will introduce 3D bioprinting methods for fabricating bioengineered blood vessel models, which can serve as the basis for treating and preventing various vascular diseases. Additionally, we will describe possible advancements from tubular to vascular models. Last, we will discuss specific applications, limitations, and future perspectives of fabricated BMs.
Biomolecular Condensates in Myeloid Leukemia: What Do They Tell Us?
Authors: Zivojin Jevtic, Melanie Allram, Florian Grebien, Juerg Schwaller
Journal: HemaSphere (2023)

Recent studies have suggested that several oncogenic and tumor-suppressive proteins carry out their functions in the context of specific membrane-less cellular compartments. As these compartments, generally referred to as onco-condensates, are specific to tumor cells and are tightly linked to disease development, the mechanisms of their formation and maintenance have been intensively studied. Here we review the proposed leukemogenic and tumor-suppressive activities of nuclear biomolecular condensates in acute myeloid leukemia (AML). We focus on condensates formed by oncogenic fusion proteins including nucleoporin 98 (NUP98), mixed-lineage leukemia 1 (MLL1, also known as KMT2A), mutated nucleophosmin (NPM1c) and others. We also discuss how altered condensate formation contributes to malignant transformation of hematopoietic cells, as described for promyelocytic leukemia protein (PML) in PML::RARA-driven acute promyelocytic leukemia (APL) and other myeloid malignancies. Finally, we discuss potential strategies for interfering with the molecular mechanisms related to AML-associated biomolecular condensates, as well as current limitations of the field.
Somatic gain-of-function mutations in BUD13 promote oncogenesis by disrupting Fbw7 function
Authors: Jianfeng Chen, Xinyi Zhang, Xianming Tan, Pengda Liu
Journal: The Journal of Experimental Medicine (2023)

Somatic mutations occurring on key enzymes are extensively studied and targeted therapies are developed with clinical promises. However, context-dependent enzyme function through distinct substrates complicated targeting a given enzyme. Here, we develop an algorithm to elucidate a new class of somatic mutations occurring on enzyme-recognizing motifs that cancer may hijack to facilitate tumorigenesis. We validate BUD13-R156C and -R230Q mutations evading RSK3-mediated phosphorylation with enhanced oncogenicity in promoting colon cancer growth. Further mechanistic studies reveal BUD13 as an endogenous Fbw7 inhibitor that stabilizes Fbw7 oncogenic substrates, while cancerous BUD13-R156C or -R230Q interferes with Fbw7Cul1 complex formation. We also find this BUD13 regulation plays a critical role in responding to mTOR inhibition, which can be used to guide therapy selections. We hope our studies reveal the landscape of enzyme-recognizing motif mutations with a publicly available resource and provide novel insights for somatic mutations cancer hijacks to promote tumorigenesis with the potential for patient stratification and cancer treatment.
Association of Nighttime Speed Limits and Electric Scooter–Related Injuries
Authors: Rasmus Liukkonen, Heljä Aarnikko, Pekka Stenman, Sanna Ovaska, Aleksi Reito
Journal: JAMA Network Open (2023)

This cohort study investigates whether nighttime speed restrictions are associated with the incidence of electric scooter–related injuries in Finland.
COVID-19 vaccine effectiveness against symptomatic infection and hospitalisation in Belgium, July 2021 to May 2022
Authors: Toon Braeye, Joris A F van Loenhout, Ruben Brondeel, Veerle Stouten, Pierre Hubin, Matthieu Billuart, Pui Yan Jenny Chung, Mathil Vandromme, Chloé Wyndham-Thomas, Koen Blot, Lucy Catteau
Journal: Eurosurveillance (2023)

Background The Belgian COVID-19 vaccination campaign aimed to reduce disease spread and severity. Aim We estimated SARS-CoV-2 variant-specific vaccine effectiveness against symptomatic infection (VEi) and hospitalisation (VEh), given time since vaccination and prior infection. Methods Nationwide healthcare records from July 2021 to May 2022 on testing and vaccination were combined with a clinical hospital survey. We used a test-negative design and proportional hazard regression to estimate VEi and VEh, controlling for prior infection, time since vaccination, age, sex, residence and calendar week of sampling. Results We included 1,932,546 symptomatic individuals, of whom 734,115 tested positive. VEi against Delta waned from an initial estimate of 80% (95% confidence interval (CI): 80–81) to 55% (95% CI: 54–55) 100–150 days after the primary vaccination course. Booster vaccination increased initial VEi to 85% (95% CI: 84–85). Against Omicron, an initial VEi of 33% (95% CI: 30–36) waned to 17% (95% CI: 15–18), while booster vaccination increased VEi to 50% (95% CI: 49–50), which waned to 20% (95% CI: 19–21) 100–150 days after vaccination. Initial VEh for booster vaccination decreased from 96% (95% CI: 95–96) against Delta to 87% (95% CI: 86–89) against Omicron. VEh against Omicron waned to 73% (95% CI: 71–75) 100–150 days after booster vaccination. While recent prior infections conferred higher protection, infections occurring before 2021 remained associated with significant risk reduction against symptomatic infection. Vaccination and prior infection outperformed vaccination or prior infection only. Conclusion We report waning and a significant decrease in VEi and VEh from Delta to Omicron-dominant periods. Booster vaccination and prior infection attenuated these effects.
Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis
Authors: Hanyu Xie, Ziyue Qin, Ziji Ling, Xiao Ge, Hang Zhang, Shuyu Guo, Laikui Liu, Kai Zheng, Hongbing Jiang, Rongyao Xu
Journal: International Journal of Oral Science (2023)

Abstract Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis ( P. gingivalis ), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis -accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis -induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis -infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis -accelerated atherosclerosis. Therapeutically, we develop P.gingivalis -pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Assessment of Disability and Depression Following Amputation Among Adults in Korea
Authors: Wonyoung Jung, Miso Kim, Hong Jin Jeon, Won Hyuk Chang, Jung Eun Yoo, Kyungdo Han, Dong Wook Shin
Journal: JAMA Network Open (2023)

This nationwide, population-based, retrospective cohort study assesses the risk of depression following amputation among adults in Korea.
Obesity and prostate cancer screening, incidence, and mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Lauren M Hurwitz, Nadine Dogbe, Kathryn Hughes Barry, Stella Koutros, Sonja I Berndt
Journal: JNCI Journal of the National Cancer Institute (2023)

Though obesity, measured by body mass index (BMI), is an established risk factor for several cancer sites, there is conflicting evidence on whether obesity increases prostate cancer risk or mortality and, if it does, whether it increases risk directly or indirectly by affecting prostate cancer screening efficacy.
External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources
Authors: Aparna C. Swaminathan, Laurie D. Snyder, Hwanhee Hong, Susanna R. Stevens, Alexander S. Long, Eric Yanchenko, Ying Qiu, Rong Liu, Hongtao Zhang, Aryeh Fischer, Leah Burns, Lisa M. Wruck, Scott M. Palmer
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, but the direct comparability of ECs versus concurrent controls is unknown.
Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints
Authors: Jiaying Lu, Xiaoxi Ma, Huiwei Zhang, Zhenxu Xiao, Ming Li, Jie Wu, Zizhao Ju, Li Chen, Li Zheng, Jingjie Ge, Xiaoniu Liang, Weiqi Bao, Ping Wu, Ding Ding, Tzu-Chen Yen, Yihui Guan, Chuantao Zuo, Qianhua Zhao, Keliang Chen, Langfeng Shi, Wanqing Wu, Yan Zhou, Yan Zhang, Fang Pei
Journal: Translational Neurodegeneration (2023)

Gaining more information about the reciprocal associations between different biomarkers within the ATN (Amyloid/Tau/Neurodegeneration) framework across the Alzheimer's disease (AD) spectrum is clinically relevant. We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography (PET) ATN biomarkers in subjects with cognitive complaints.
Disordered Eating Attitudes and Food Choice Motives Among Individuals Who Follow a Vegan Diet in Brazil
Authors: Bruna Caruso Mazzolani, Fabiana Infante Smaira, Gabriel P. Esteves, Martin Hindermann Santini, Alice Erwig Leitão, Heloísa C. Santo André, Bruno Gualano, Hamilton Roschel
Journal: JAMA Network Open (2023)

Importance It remains controversial whether adhering to a vegan diet may be associated with a higher prevalence of disordered eating. Also, main food choice motives and their association with disordered eating in this population are still unknown. Objective To determine the association between disordered eating attitudes and food choice motives of individuals who follow a vegan diet. Design, Setting, and Participants This is a cross-sectional online survey conducted between September 2021 and January 2023. Individuals of both sexes, aged 18 years or older, following a vegan diet for at least 6 months, currently living in Brazil were recruited through advertisements on social media. Exposure Adherence to a vegan diet and food choice motives. Main Outcomes and Measures Disordered eating attitudes and food choice motives. Results Nine hundred seventy-one participants completed the online survey. Median (IQR) age and BMI of participants was 29 (24-36) years and 22.6 (20.3-24.9), respectively, and 800 participants (82.4%) were female. Most participants (908 respondents [94%]) were categorized with the lowest level of disturbed eating attitudes. “Need and hunger,” “liking,” “health,” “habits,” and “natural concerns” were the most important food choice motives in this population, while “affect regulation,” “social norms,” and “social image” were the less important ones. Adjusted models showed that “liking,” “need and hunger,” and “health” were associated with lower levels of disordered eating attitudes, while “price,” “pleasure,” “sociability,” “traditional eating,” “visual appeal,” “social norms,” “social image,” “weight control,” and “affect regulation” were associated with higher levels of disordered eating attitudes. Conclusions and Relevance In this cross-sectional study, as opposed to previous suggestions, levels of disordered eating were very low among vegans, although certain food choice motives were associated with disordered eating attitudes. Understanding the motivations of adhering to diets that may impose restrictions, which include vegan diets, may help tailor interventions focused on promoting healthy eating and preventing or treating disordered eating.
Use of direct microscopy to diagnose superficial mycoses: a survey of UK dermatology practice
Authors: David J Chandler, Reika Yamamoto, Rod J Hay
Journal: British Journal of Dermatology (2023)

Direct microscopy is a useful tool in the diagnosis of superficial mycoses; however, it is a fading skill among UK dermatologists. Most dermatologists do not have access to a working microscope, and do not feel confident to perform the procedure or interpret the microscopic findings.
A novel risk signature for predicting brain metastasis in patients with lung adenocarcinoma
Authors: Yanyan Zhao, Shen Gu, Lingjie Li, Ruping Zhao, Shujun Xie, Jingjing Zhang, Rongjing Zhou, Linglan Tu, Lei Jiang, Shirong Zhang, Shenglin Ma
Journal: Neuro-Oncology (2023)

Abstract Background Brain metastasis (BM) are a devastating consequence of lung cancer. This study was aimed to screen risk factors for predicting BM. Methods Using an in vivo BM preclinical model, we established a series of lung adenocarcinoma (LUAD) cell subpopulations with different metastatic ability. Quantitative proteomics analysis was used to screen and identify the differential protein expressing map among subpopulation cells. Q-PCR and Western-blot were used to validate the differential proteins in vitro. The candidate proteins were measured in LUAD tissue samples (n = 81) and validated in an independent TMA cohort (n = 64). A nomogram establishment was undertaken by performing multivariate logistic regression analysis. Results The quantitative proteomics analysis, qPCR and Western blot assay implied a five-gene signature that might be key proteins associated with BM. In multivariate analysis, the occurrence of BM was associated with age ≤ 65 years, high expressions of NES and ALDH6A1. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.934 (95% CI, 0.881–0.988) in the training set. The validation set showed a good discrimination with an AUC of 0.719 (95% CI, 0.595–0.843). Conclusions We have established a tool that is able to predict occurrence of BM in LUAD patients. Our model based on both clinical information and protein biomarkers will help to screen patient in high-risk population of BM, so as to facilitate preventive intervention in this part of the population.
Probiotic: is diet part of the efficacy equation?
Authors: Héloïse Rytter, Emilie Combet, Benoit Chassaing
Journal: Gut Microbes (2023)

Discovered at the beginning of the 20th century by Nobel laureate Élie Metchnikoff, probiotics have more recently emerged as a potential noninvasive therapeutic approach for the treatment of various chronic diseases. However, recent population-based clinical studies suggest that probiotics are often ineffective and may even exhibit potential deleterious effects. Hence, a deeper molecular understanding of strain-specific beneficial effects, together with the identification of endogenous/exogenous factors modulating probiotic efficacy, is needed. The lack of consistency in probiotic efficacy, together with the observation that numerous preclinical findings on probiotics are not translating once applied to humans through clinical trials, suggests a central role for environmental factors, such as dietary patterns, in probiotic efficacy. Two recent studies have been instrumental in filling this knowledge gap, defining the role played by diet in probiotic efficacy on metabolic deregulations in both mouse models and humans .